Studies are designed to gain a more complete understanding of the sequence of molecular events involved in the action of insulin on fat cells. Insulin has been shown to initiate its actions on target tissues by interacting with specific receptors on the surface of the cell membrane. The metabolic events occurring immediately subsequent to this interaction are largely unknown. Fruitful information should be obtained concerning this (polyamines, vitamin K5, H202) which are capable of stimulating hexose transport across the plasma membrane. These compounds are well suited for these studies since they mimic the action of insulin at a point subsequent to the insulin-receptor interaction. In addition studies of adipocytes in culture will be conducted in an attempt to define those factors and processes which chronically modulate basal and insulin-stimulated glucose transport. A second aim is to extend our studies on the cellular alterations responsible for altered insulin sensitivity in several clinical disorders and metabolic states. These states include diabetes, obesity, glucocorticoid excess and fasting. Cellular processes in adipocytes to be assessed include specific insulin binding and affinity of the hormone for binding, basal and insulin-stimulated glucose transport and intracellular glucose metabolism.